The proposed investigation examines the alteration of subpopulations of cytochrome P-450, the collective name for a small group of closely related hemoproteins involved in the oxidative metabolism of many xenobiotics and procarcinogens. The unique approach to be used centers around the relative abilities of the cytochrome subpopulations to form spectrally detectable metabolic-intermediate complexes during the metabolism of 4 classes of nitrogenous compounds and the non-nitrogenous methylenedioxyphenyl compounds. The consequences of subpopulation alterations, and the specificity of inhibition by metabolic-intermediate complexes, on the monooxygenase reactions will be investigated. Studies showing differing rates of metabolic-intermediate complex formation in various tissues under induced or other conditions, and studies using the extent of cytochrome P-450 involvement in complex formation to "type" the two forms of rabbit lung cytochrome P-450, indicate the feasibility of the approach. Four specific areas of investigation have been delineated. One area will be a complete examination of the form (s) of hepatic cytochrome P-450 induced by SKF 525-A, a compound which also forms metabolic-intermediate complexes. A second area will examine pulmonary cytochrome P-450 subpopulations in rat, before and after exposure to polycyclic hydrocarbons. Also, in both rat and rabbit, attempts will be made to induce or alter the subpopulations by compounds capable of forming metabolic-intermediate complexes in that tissue. A third area will examine the stability of all forms of metabolic-intermediate complexes in vitro in an attempt to define the parameters necessary for their formation and/or accumulation in vivo. The fourth area will extend the range of compounds using for "typing" of the cytochromes, and this increased arsenal will be used to investigate cytochrome P-450 subpopulations after liver and lung toxins, or with changes in physiological status.